Sister chromatid exchanges in adult epileptic patients on phenytoin therapy

Sister chromatid exchanges (SCE) were studied in lymphocyte cultures of 12 adult male epileptic patients on long-term monotherapy with phenytoin (PHT) and of matched controls. Significantly increased frequency of SCE was observed in the epileptic patients as a group and in almost all individuals, indicating a detectable chromosome damaging effect of PHT therapy on its human users.     

Isoenzymes of alkaline phosphatase in epileptic patients receiving carbamazepine monotherapy.

The effects of carbamazepine monotherapy were investigated in 20 female and 21 male epileptic patients to determine whether treatment would induce an increase in serum alkaline phosphatase (ALP) activity, a known effect of many anticonvulsant drugs. Serum total ALP activity was increased in nine out of the 41 patients (22%), serum bone ALP activity was increased in 10 (24%), and serum non-bone ALP activity was increased in three (7%). There was no significant difference when the mean of the patients' serum total ALP was compared with that of the controls. Twenty per cent of the patients with increased serum bone ALP had normal serum total ALP, indicating that increased serum bone isoenzyme activity may precede an increase in the total enzyme activity. This should be considered when interpreting results of increased total ALP in epileptic patients.     

II. An altered proliferation response due to the anticonvulsant phenytoin (PHT) in epileptic patients

Lymphocyte proliferation kinetics (LPK) is an end point used in genetic toxicology that was proposed as an alternative for the screening of anticonvulsant drugs. The effect of phenytoin (PHT) was investigated on the mitotic and proliferation indices in cultured blood lymphocytes of 33 sporadically collected untreated and 42 PHT-treated epileptics, where the duration of treatment was 3, 6, and 9 months, and 40 control subjects (age range 10-30 years). PHT induced mitotic delays and decreased the mitotic index. A significant heterogeneity of the first, second and the third metaphases between treated and untreated groups was revealed. A reduction of the proliferation index (P < 0.001) and proliferation delay per cycle (P < 0.001) was also observed. There was little variation between the controls and untreated patients (P > 0.05). The results have confirmed that PHT can affect responses leading to genotoxicity. Teratogenesis Carcinog. Mutagen. 21:151-164, 2001.     

Psychologic vulnerability in epileptic patients.

The psychologic vulnerability of the epileptic patient over the course of the disease pertains largely to the issues of control and competence. These difficulties are especially apparent during late adolescence and early adulthood. If there is no successful sphere of operation outside the family, a malignant intrafamilial adaptation can occur that is severely limiting for both the patient and his or her family. This paper suggests ways to cope with these psychologic problems.     

丙戊酸对癫痫患儿骨代谢影响的Meta分析

目的采用Meta分析方法定量分析丙戊酸对癫痫患儿骨代谢的影响。方法电子检索中国维普科技期刊数据库、万方数据库、中国知网、中国生物医学文献数据库、EMCC、PubMed、OVID及Cochrance图书馆,纳入丙戊酸对癫痫患儿骨代谢影响的观察性研究,采用NOS量表评估纳入文献的质量。采用RevMan5．2软件进行Meta分析。结果14篇文献（英文10篇,中文4篇）进入Meta分析,均为病例对照研究,累计病例组507例,对照组480例。Meta分析结果显示,丙戊酸对血钙（MD=0．0l,95％CI：-0．05—0．06,P=0．13）、血磷（MD=-0．03,95％CI：-0．19—0．13,P=0．67）、碱性磷酸酶（MD=0．37,95％CI：-19．02～19．77,P=0．97）无明显影响,但丙戊酸组骨密度低于对照组,MD=-0．03,95％CI：-0．06～-0．00,P=0．03;丙戊酸组甲状旁腺激素水平显著高于对照组,MD=4．83,95％CI：1．15～8．50,P=0．01;丙戊酸组25-羟维生素D水平显著低于对照组,MD=-2．46,95％CI：-4．37～-0．55,P=0．01。结论现有证据表明,丙戊酸对癫痢患儿血钙、血磷和ALP无显著影响．但对骨密度、25-OH—VtiD和PTH有影响。     

Lymphocytotoxins in a Chronic Hemodialysis Population

Patients in a chronic hemodialysis program were studied over a period of 2½ years to determine whether or not blood transfusions cause the development of cytotoxic antibodies. Blood exposure was moderate in quantity and varied in the type of processing used. No patient was demonstrated to have converted from negative serum cytotoxicity to positive serum cytotoxicity on the basis of blood transfusions given while on dialysis. The use of leukocyte-free blood, although theoretically desirable, was not shown to be necessary by this study.     

Cold Lymphocytotoxins in Infections and Parasitic Infestations

'Cold'lymphocytotoxins were studied in sera of viral infections (mumps, influenza, rubella, herpes, infectious mononucleosis), Rickettsia and Mycoplasma pneumoniae infections and sera from infestations by toxoplasmosis, by endointestinal parasites and parasites with tissue migration. All sera positive at + 37° C were eliminated. A score was established in order to compare the sera with each other. The frequency of 'cold'cytotoxins varies according to the type of infection under study. It is especially high in infectious mononucleosis, mumps, Mycoplasma pneumoniae infections and migrating parasite infestations. In these same disorders, the greatest number of high scores can be found (a single exception being the high scores in herpes). According to the serum, cold cytotoxins give every possible score for the same disease. Thus, it would seem that the same antibodies are always involved, but in varying degrees of strength.     

Lymphocytotoxins in leprosy and in asymptomatic hepatitis B virus infection.

Serum lymphocytotoxic antibodies (LCAs) were detected in 67% of Papua New Guinean lepromatous leprosy patients who were persistent carriers of hepatitis B surface antigen (HBsAg). Lymphocytotoxins were not associated with asymptomatic HBsAg in either healthy controls or tuberculoid leprosy patients. It was apparent that, although HBsAg itself is a poor indicator of in vitro lymphocytotoxicity, when the antigen occurred in a host with impaired immune response, lymphocytotoxicity, when the antigen occurred in a host with impaired immune response, lymphocytotoxicity was enhanced. In contrast to this finding, lepromatous leprosy patients without HBsAg had significantly depressed LCA production in comparison with tuberculoid patients and controls. The interaction between leprosy and hepatitis B virus was highly significant (P = 0.001) in an analysis of variance of cytotoxicity scores. It is proposed that the previously reported equivocal results regarding autoantibodies in leprosy patients may be explained by this unusual interaction between lepromatous leprosy and hepatitis B virus infection.     

Genotoxicity of the anticonvulsant drug phenytoin (PHT): a follow-up study of PHT-untreated epileptic patients. I. Sister chromatid exchange (SCE) analysis.

Phenytoin (PHT) is a widely prescribed antiepileptic drug. Its potential to interact with genetic material was investigated in a set of 30 epileptic patients (age 10-30 years) prior to and following the administration of PHT over a period of 9 months (grouped in a multiple of 3 months) and 40 control subjects in relation to age, sex, duration of drug therapy, and plasma concentration of PHT, using the sister chromatid exchange (SCE) frequency assay. Plasma levels of the phenytoin were measured by biochemical assay in epileptic patients before and after the PHT therapy. The peripheral blood lymphocytes were cultured and harvested at 72 h. The frequency of SCE was significantly higher (P < 0.001) in both age groups (10-20 and 21-30 years) for PHT-treated epileptics compared to PHT-untreated and control subjects. However, there were no considerable variations in SCE finding between the control and PHT-untreated patients. Between the two age groups, a significantly higher SCE frequency was observed in PHT-treated patients (P < 0.01) in the older age group (21-30 years). Mean SCE frequency did not differ between the male and female in the controls, PHT-untreated, or treated epileptics. Correlation between the plasma concentration of PHT and the incidence of SCE among 30 patients was insignificant. PHT monotherapy appears to have genotoxic effect as expressed by the induction of increased SCE rates in treated epileptics, while disease does not play any role in inducing genetic damage as shown by no difference in SCE frequencies between control subjects and PHT-untreated epileptic patients.     

Genotoxicity of the anticonvulsant drug phenytoin (PHT): a follow-up study of PHT-untreated epileptic patients. II. Mitotic index (MI) and proliferation kinetics.

The mitotic index and proliferation rate index were investigated to determine the effect of phenytoin (PHT) in cultured blood lymphocytes of epileptics prior to and following administration of PHT over a period of 9 months (grouped in multiples of 3 months) and 40 control subjects (age range 10-30 years). Treatment with PHT brought inhibition of the mitotic index (MI) and proliferation rate index (PRI), which were significantly higher in treated subjects or which were more expressive in treated lymphocytes (P < 0.001) for all the three durations of treatment. In addition, statistically significant heterogeneity of first, second, and third metaphases between the treated, untreated, and control subjects was found. Mean PRI values were used to estimate cell cycle delays, showing the highest effect in treated lymphocytes (P < 0.001). There was no considerable variation between the control and untreated (P > 0.05). The study demonstrates that PHT may be potentially genotoxic and hence the usefulness of MI and PRI in monitoring epileptics on anticonvulsant treatment.     

Granuloma formation in patients receiving BCG immunotherapy.

Eleven patients with acute myeloblastic leukaemia have received repeated intravenous injections of BCG containing 4-9 X 10(6) live organisms per millilitre. Non-caseating epithelioid granulomas, sometimes with giant-cell formation, have been demonstrated in eight bone marrow aspirates. Seven patients had granulomas in the liver, three in the lung, one in the spleen, one in lymph nodes, and one in a skin biopsy. One patient had a raised serum alkaline phosphatase, but none of the patients had any illness which could be related to the presence of granulomas. Granuloma formation appeared more extensive in four patients who were probably anergic before BCG treatment. Until the significance of this finding becomes clear great care should be taken when giving BCG by the intratumour of intravenous routes to potentially immunoincompetent patients.     

''Double marker'' lymphocytes in patients receiving tetracycline.

When T and B cell counts, using sheep cell rosettes and surface immunoglobulin as markers, are done on the lymphocytes of individuals who are receiving tetracycline, unusually high numbers of 'double marker' cells are regularly found.     

癫痫手术治疗的皮层电图监测

目的：探讨皮层电图（ＥＣｏＧ）监测对切除癫痫病灶的应用价值及适应症。方法：对１０４例难治性癫痫患者使用盘状电极行ＥＣｏＧ监测下切除癫痫灶进行研究。结果：术前脑电图（ＥＥＧ）检查８６例异常（８２７％）。皮层电图１０２例异常（９８％）。术后随访３个月至４年,有８８例（８４６％）临床发作已控制,１６例发作次数明显减少。复查常规ＥＥＧ有痫样放电６例,慢波局限性改变５例,其余ＥＥＧ均为正常。术前术后ＥＥＧ阳性率相差显著。结论：在ＥＣｏＧ监测下切除癫痫灶具有一定的临床价值     

Seroepidemiological observation of Taenia solium cysticercosis in epileptic patients in Korea.

Prevalence survey of neurocysticercosis was made in a mixed epilepsy patients of Changmi Club in Korea. From February 1987 to July 1990, a total of 2,667 randomly selected patients at 27 local centers was tested for their serum levels of anti-Cysticercus antibody (IgG) by enzyme-linked immunosorbent assay. Positive rate of the antibody was 4.0% in the examined patients. The standardized antibody positive rate by provincial population was 3.1%. The rate was the highest in patients living in Cheju Do (8.4%). The patient age brackets of 0 approximately 9 years and over 50-year showed higher positive rates of the antibody. In 750 normal persons who checked up routine physical examination, the antibody positive rate was 2.1% (standardized rate was 1.8%). These seroepidemiological data disclosed for the first time the prevalence of cysticercosis in epileptic patients and in population.     

癫痫患者免疫状态的探讨

本文观察了７０例癫痫（ＥＰ）患者的免疫状态，首次检测了Ｂ淋巴细胞亚群，ｓＩＬ－２Ｒ及ＴＮＦ，对各项免疫学指标进行了对比研究，发现ＩｇＡ，ＩｇＭ含量明显降低，ＣＩＣ含量明显增高（Ｐ＜０．０１），Ｃ３明显降低（Ｐ＜０．０５），显示患者体液免疫功能低下；淋巴细胞亚群测定发现ＣＤ３＾＋，ＣＤ４＾＋明显降低，ＣＤ８＾＋明显增高，ＣＤ４＾＋／ＣＤ８＾＋比值明显低于对照组（Ｐ＜０．０１），表明细胞免疫功能低下；     

Lymphocytotoxins in acute and chronic hepatitis. Characterization and relationship to changes in circulating T lymphocytes.

Serum lymphocytotoxicity (LCT) was detected in 49% of fifty-one patients with acute viral hepatitis and 72% of twenty-nine patients with chronic hepatitis. LCT was not detected in ten chronic carriers of hepatitis B surface antigen. Characterization of LCT revealed it to be active at physiologic temperatures and to be reactive against both T and B lymphocytes. The occurrence of LCT was transient in acute hepatitis and intermittent in chronic hepatitis. There was a significant inverse relationship between the percentage change in LCT over time and peripheral blood T-cell proportions amongst the patients studied. These findings indicate the importance of liver damage in the appearance of LCT and suggest that LCT may contribute to depressed lymphocyte function in liver disease.     

Anemia in HIV-infected patients receiving highly active antiretroviral therapy.

BACKGROUND: Anemia is common in HIV infection, particularly in advanced disease states. We wished to determine how highly active antiretroviral therapy (HAART) and other factors affected the level of hemoglobin in HIV infection. METHODS: We analyzed data from 905 patients receiving care at Johns Hopkins in Baltimore, Maryland after July 1, 1996. Analyses were done of hemoglobin levels obtained at baseline and during 1 year of follow-up in patients who received and did not receive a HAART regimen. Use of HAART and other demographic and clinical factors were examined. RESULTS: Eleven percent of patients had a hemoglobin count <10 g/dL, 27% had a hemoglobin count 10 to 12 g/dL, and 21% had a hemoglobin count of >14 g/dL at baseline before HAART was started. During 1 year of follow-up, use of HAART was associated with a hemoglobin levels >14 g/dL in 42% of patients, irrespective of use of zidovudine as part of HAART regimen, compared with 31% of patients who did not use HAART. In multivariate analysis, use of HAART was strongly associated with not having anemia during 1 year of follow-up, adjusting for patient gender, race, injection drug use history, baseline CD4 and HIV-1 RNA levels, and anemia treatments. CONCLUSIONS: HAART is an effective treatment of the anemia of HIV infection. Patients who continue to have symptomatic anemia while receiving HAART may need additional intervention.